DESCRIPTION (Adapted from the applicant's abstract and specific aims): An elevated low density lipoprotein (LDL) cholesterol (C) (>160 mg/dl) is a major risk factor for coronary heart disease. The strictest diet recommended for LDL-C lowering prior to use of drugs in patients with elevated LDL-C values is the step 2 diet (<30% fat, <7% saturated fat, <200 mg of cholesterol/day). We have previously studied 46 middle aged and elderly men and post-menopausal women (mean age 62, range 41-81) with either normal (14 men, 10 women) or elevated LDL-C (10 men and 12 women) on an average U.S. diet (35% fat, 14% saturated fat, 14% monounsaturated fat, 7% polyunsaturated fat, 147 mg cholesterol/1000 calories, 15% protein, 49% carbohydrate) under controlled conditions for 6 weeks and then on a step 2 diet for 6-24 weeks (26% fat, 4% saturated fat, 11% monounsaturated fat, 10% polyunsaturated fat, 45 mg cholesterol/1000 calories, 16% protein, 58% carbohydrate) under controlled isoweight conditions with all food and drink provided. Mean LDL-C lowering was 16.9% (range + 5.5 to -39.7%) and mean HDL-C lowering was 14.2% (range + 6.3 to -29.7%), with similar alterations in apolipoprotein (apo) A-I and B. At the end of each diet phase subjects received their food in 20 hourly feedings, and received a bolus injection (10 umol/kg) followed by a primed constant infusion of [2H3] leucine (10 umol/kg/hr) over 15 hours. Twelve subjects also received a bolus of [13C2] leucine (26.8 umol/kg) and in addition to blood samples at 0, 1-4, 6, 8, 10, 12, and 15 hours of the infusion, also had blood samples drawn at 24, 48, 72, and 96 hours. All subjects also received 1.2 g of deuterium oxide/kg body water as an oral bolus at the beginning of the infusion for the measurement of cholesterol kinetics. 19 younger men and women (mean age 28, range 23-41) were also studied while on an average U.S. Diet. The major objectives of this research study are to determine plasma cholesterol kinetics and apolipoprotein kinetics (apoA-IV, B-48, B-100, C-II, C-III, and E within d<1.006-1.019 g/ml and 1.019-1.063 g/ml or LDL, and apoA-I and apoA-II within d 1.063-1.21 g/ml or HDL and Lp(a)) by isotope ratio or gas chromatographic mass spectrometry. Lipoproteins have been isolated by ultracentrifugation, and apo mass will be determined by ELISA. Kinetic analysis will be carried out using multicompartmental analysis. The major aims are to relate the marked variability in LDL-C, HDL-C, apoA-I and apoB lowering in response to diet to alterations in these kinetic parameters in 46 subjects as well as to examine effects of age, gender, body mass index, menopausal status, lipoprotein composition, apoA-IV and apoE genotype, LDL size, and HDL size on lipoprotein metabolism in 65 subjects.